Autoimmune Liver Disease

The Importance of Epidemiology in Determining Environmental Causes

By Elaine Moore

A better understanding of the populations primarily affected by autoimmune liver diseases can help elicit the environmental triggers of these disorders.

Autoimmune liver (hepatic) diseases include primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). In addition, a number of systemic autoimmune disorders such as sarcoidosis and systemic lupus erythematosus (SLE) can result in liver disease. Unfortunately however, although autoimmune liver disorders were discovered more than a hundred years ago, little is known about their epidemiology or distribution throughout the world. A better understanding of the populations affected by these disorders would contribute to our understanding of their environmental triggers.


Most studies relating to the epidemiology of autoimmune liver diseases have focused on primary biliary cirrhosis and of sarcoidosis of the liver. In both of these conditions, the incidence in Sweden and Norway are fairly high when compared to cases reported outside of northern Europe. In addition, the incidence of PBC in Australia and Canada is lower than the incidence in England despite the strong British heritages seen in both countries.

Data on all three autoimmune liver diseases show the incidence to be much lower in people of Asian descent compared to those of European descent. Studies also show that African-American patients with autoimmune hepatitis are more likely to progress to cirrhosis than Caucasians affected with autoimmune hepatitis. More research is needed to understand the reasons behind these discrepancies.

Familial Association

Patients with primary sclerosing cholangitis tend to have a stronger familial association than patients with other autoimmune liver diseases. And although men between 20 and 40 years of age are most likely to be affected, an increased incidence of PSC has recently been reported in children, including infants. Compared to the general population, PBC is more likely to occur in families although the genetic link is lower than that seen in PSC. The greatest familial association seen in PBC occurs in mothers and daughters. Autoimmune hepatitis has the weakest familial association among the autoimmune liver diseases. However, people with autoimmune hepatitis are more likely to have a family member with autoimmune diseases in general.

Genetic Factors

The three autoimmune diseases have been intensively studied for links to immune system markers. The most common finding has been with HLA-DR8 acting as a risk factor for primary biliary cirrhosis. However, the link is not as strong as that seen with other autoimmune diseases. Among patients with autoimmune hepatitis the strongest link is seen with HLA DR3/DR4, and in primary sclerosing cholangitis the strongest link is with DRw52a.

Autoimmune Disease Influences

The autoimmune liver diseases have also been studied for their association with other autoimmune diseases. The strongest link has been found with primary sclerosing cholangitis occurring in patients with inflammatory bowel disease. A strong link also occurs between people with autoimmune thyroid disease and autoimmune hepatitis, and with primary biliary cirrhosis and the disorders autoimmune thyroid disease and systemic lupus erythematosus.

Environmental Factors

Studies have shown a lower incidence of the inflammatory bowel disorder ulcerative colitis occurring among smokers and among people who had a previous appendectomy. Because of the link between inflammatory bowel disease and PSC, researchers studied these risk factors in PSC. Their investigations showed a lower incidence of PSC among smokers and no influence from previous appendectomy.

Primary biliary cirrhosis has also been reported to be associated with cancer, particularly breast cancer. The risk of hepatocellular cancer is also high in patients with PBC as it is in patients with cirrhosis from any cause.

Recent reports have shown a marked association between 2-nonynoic acid, a cosmetic ingredient and primary biliary cirrhosis, a disease 9 times more likely to occur in women. Other suspected triggers of PBC include smoking, bacterial and retroviral proteins, hormone replacement therapy, and the use of nail polish. It’s thought that chemical degradation in the liver causes a loss of immune tolerance that predisposes women to developing PBC. Similarly, a process of molecular mimicry induced by hepatitis viruses, is suspected of triggering autoimmune hepatitis.

However, a better understanding of the epidemiology of autoimmune liver diseases is necessary to unearth a complete listing of the various environmental factors that contribute to autoimmune liver disease as well as those that offer protection. ♦

© 4 Jun 2007 Copyrighted by Elaine Moore


JJ Feld and EJ Heathcote, Epidemiology of Autoimmune Liver Disease, J Gastroenterol Hepatol 2003; 18(10): 1118-1128.

Elaine Moore, Autoimmune Diseases and Their Environmental Triggers, Jefferson, NC: McFarland and Company, 2002.

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